chr7-87941395-G-C

Variant names:

• chr7-87941395-G-C
• rs470
• NM_001324418.2:c.246+6209G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001324418.2(ADAM22):​c.246+6209G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM22 NM_001324418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 6 publications found

Genes affected

ADAM22 (HGNC:201): (ADAM metallopeptidase domain 22) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Unlike other members of the ADAM protein family, the protein encoded by this gene lacks metalloprotease activity since it has no zinc-binding motif. This gene is highly expressed in the brain and may function as an integrin ligand in the brain. In mice, it has been shown to be essential for correct myelination in the peripheral nervous system. Alternative splicing results in several transcript variants.[provided by RefSeq, Dec 2010]

ADAM22 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 61

  Inheritance: Unknown, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324418.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM22	NM_001324418.2	MANE Select	c.246+6209G>C		intron	N/A	NP_001311347.1	H7C3I4
	ADAM22	NM_001324419.2		c.243+6209G>C		intron	N/A	NP_001311348.1
	ADAM22	NM_001391975.1		c.246+6209G>C		intron	N/A	NP_001378904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM22	ENST00000413139.2	TSL:5 MANE Select	c.246+6209G>C		intron	N/A	ENSP00000412085.2	H7C3I4
	ADAM22	ENST00000265727.11	TSL:1	c.246+6209G>C		intron	N/A	ENSP00000265727.7	Q9P0K1-1
	ADAM22	ENST00000398209.7	TSL:1	c.246+6209G>C		intron	N/A	ENSP00000381267.3	Q9P0K1-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs470; hg19: chr7-87570710;